Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis

J Clin Pathol. 2015 Dec;68(12):1036-9. doi: 10.1136/jclinpath-2015-203083. Epub 2015 Jul 22.

Abstract

Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs.

Keywords: AUDIT; COLORECTAL CANCER; QUALITY ASSURANCE.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Costs and Cost Analysis
  • DNA Mismatch Repair / genetics*
  • Genetic Testing / economics
  • Genetic Testing / methods
  • Germ-Line Mutation* / genetics
  • Humans
  • Immunohistochemistry / economics
  • Mass Screening / economics
  • Mass Screening / methods
  • Medical Audit / economics
  • Microsatellite Instability
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Referral and Consultation
  • Retrospective Studies

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf